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多组学揭示二甲双胍在肠道微生物群重塑和肝脏代谢重编程以干预非酒精性脂肪性肝病中的双重作用。

Multiomics reveals metformin's dual role in gut microbiome remodeling and hepatic metabolic reprogramming for MAFLD intervention.

作者信息

Sun Yuan-Dong, Zhang Hao, Gong Xiao-Long, Li Yuan-Min, Han Ruiqin, Zhou Chun-Xiao, Han Jian-Jun

机构信息

Xinjiang Medical University Affiliated Cancer Hospital, Urumqi, China.

Xinjiang Key Laboratory of Translational Biomedical Engineering, Urumqi, China.

出版信息

Sci Rep. 2025 Jul 2;15(1):22699. doi: 10.1038/s41598-025-07557-7.


DOI:10.1038/s41598-025-07557-7
PMID:40594788
Abstract

Metabolic Associated Fatty Liver Disease (MAFLD), previously known as Non-Alcoholic Fatty Liver Disease, is a growing global health issue associated with obesity, type 2 diabetes, and metabolic syndrome. This study investigates the potential of metformin, a common anti-diabetic drug, to slow the progression of MAFLD using a multi-omics approach. Male Wistar rats were fed a choline-deficient diet to induce MAFLD and treated with metformin through their drinking water for 48 weeks. We conducted a comprehensive analysis including liver histology, untargeted metabolomics, lipidomics, and gut microbiome profiling to assess the effects of metformin on liver and gut metabolic patterns. Metformin administration led to significant changes in gut microbiome diversity and the abundance of specific microbial species in MAFLD rats. Histological analysis showed that metformin-treated rats had reduced lipid accumulation and fibrosis in the liver compared to untreated MAFLD rats. Metabolomic and lipidomic analyses revealed that metformin corrected abnormal lipid metabolism patterns, reduced hepatic fat deposition, and influenced key metabolic pathways associated with MAFLD progression. Our findings suggest that metformin has a protective role against MAFLD by modulating gut microbiota and liver metabolism, thereby slowing the progression of hepatic fibrosis. This study provides insights into the therapeutic potential of metformin for MAFLD by addressing metabolic pattern disorders and abnormal changes in gut microbial diversity, highlighting its impact on lipid metabolism and gut-liver axis interactions.

摘要

代谢相关脂肪性肝病(MAFLD),以前称为非酒精性脂肪性肝病,是一个日益严重的全球健康问题,与肥胖、2型糖尿病和代谢综合征相关。本研究使用多组学方法研究了常见抗糖尿病药物二甲双胍减缓MAFLD进展的潜力。给雄性Wistar大鼠喂食缺乏胆碱的饮食以诱导MAFLD,并通过饮用水用二甲双胍治疗48周。我们进行了全面分析,包括肝脏组织学、非靶向代谢组学、脂质组学和肠道微生物组分析,以评估二甲双胍对肝脏和肠道代谢模式的影响。给予二甲双胍导致MAFLD大鼠肠道微生物组多样性和特定微生物种类丰度发生显著变化。组织学分析表明,与未治疗的MAFLD大鼠相比,用二甲双胍治疗的大鼠肝脏中的脂质积累和纤维化减少。代谢组学和脂质组学分析显示,二甲双胍纠正了异常的脂质代谢模式,减少了肝脏脂肪沉积,并影响了与MAFLD进展相关的关键代谢途径。我们的研究结果表明,二甲双胍通过调节肠道微生物群和肝脏代谢对MAFLD具有保护作用,从而减缓肝纤维化的进展。本研究通过解决代谢模式紊乱和肠道微生物多样性异常变化,深入了解了二甲双胍对MAFLD的治疗潜力,突出了其对脂质代谢和肠-肝轴相互作用的影响。

相似文献

[1]
Multiomics reveals metformin's dual role in gut microbiome remodeling and hepatic metabolic reprogramming for MAFLD intervention.

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[2]
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[7]
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[10]
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本文引用的文献

[1]
Combination of Pioglitazone and Metformin Actions on Liver Lipid Metabolism in Obese Mice.

Biomolecules. 2023-7-31

[2]
A multisociety Delphi consensus statement on new fatty liver disease nomenclature.

J Hepatol. 2023-12

[3]
Age-related alterations in metabolome and microbiome provide insights in dietary transition in giant pandas.

mSystems. 2023-6-29

[4]
Chinese Visceral Adipose Index Shows Superior Diagnostic Performance in Predicting the Risk of Metabolic Dysfunction Associated Fatty Liver Disease in Early Postmenopausal Chinese Women.

Diabetes Metab Syndr Obes. 2023-3-6

[5]
An Overview of Hepatocellular Carcinoma Surveillance Focusing on Non-Cirrhotic NAFLD Patients: A Challenge for Physicians.

Biomedicines. 2023-2-16

[6]
Metformin suppresses calcium oxalate crystal-induced kidney injury by promoting Sirt1 and M2 macrophage-mediated anti-inflammatory activation.

Signal Transduct Target Ther. 2023-1-27

[7]
Research progress of metformin in the treatment of liver fibrosis.

Int Immunopharmacol. 2023-3

[8]
Metabolomics to identify fingerprints of carotid atherosclerosis in nonobese metabolic dysfunction-associated fatty liver disease.

J Transl Med. 2023-1-9

[9]
A novel lncRNA MDHDH suppresses glioblastoma multiforme by acting as a scaffold for MDH2 and PSMA1 to regulate NAD+ metabolism and autophagy.

J Exp Clin Cancer Res. 2022-12-17

[10]
Elevated serum levels of diamine oxidase, D-lactate and lipopolysaccharides are associated with metabolic-associated fatty liver disease.

Eur J Gastroenterol Hepatol. 2023-1-1

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